Project Summary/Abstract The BRAIN Initiative has made a significant investment in invasive human neuroscientific studies that take advantage of unique neurosurgical opportunities to study basic human neuroscience without therapeutic intent. These non-therapeutic studies are of particular ethical interest due to uncertainty and disagreement about when such studies should be allowed, particularly with respect to risk/benefit assessments. Such ethical issues arise since (1) these investigations expose participants to additional risks beyond that of therapeutic surgery, (2) these risks cannot be offset by any expectation of direct therapeutic benefit, (3) the neurological sequelae may be more consequential than harm to other organs, (4) the rarity of the investigative techniques results in uncertainty of the actual risks, and (5) the benefits or value of such investigations are not explicitly obvious, and given the rapid growth of this field, it may become increasingly unclear what knowledge we should value going forward as society. We hypothesize (i) that patient-participants living with disabling disorders have a unique and valuable perspective on the risks and worth of such research, (ii) that such judgements may contrast with those of investigators and the general public based on differing life experience, and (iii) that understanding these different judgments can advance the ethical design of future studies and critically broaden the field?s discussion of valuing the individual risks against the social benefit of the research. In Aim 1, we seek to understand patient-participant perspectives on risks, benefits, and permissibility of such trials. This population may have unique perspectives based on their history of chronic neurologic disease, which may uniquely influence their assessment of risks and value. We will interview patients across studies with varying degrees of invasiveness to elucidate a wide range of experiences and to evaluate the impact of invasiveness on the relevant perspectives. In Aim 2, we elucidate alternate perspectives from investigators (physicians, engineers, neuroscientists and others) as well as the public, to assess how differing social, life, and occupational experiences impact risk and benefit assessments This data and data from aim 1 will provide a wide-ranging set of comparative narratives about perceptions of risks, benefits, and the evaluations thereof. In Aim 3, we will elucidate perspectives from all three populations on the limits of the risks, benefits, and social worth of future research. Are there limits to what future scientific goals should be pursued with evolving technology in non-therapeutic studies? To address these aims, we bring together a multidisciplinary team of clinicians, ethicists, and psychologists to explore the diverse social values that inform risk/benefit assessments. The proposal is enhanced by an environment with a strong history and current portfolio of non-therapeutic invasive human neuroscientific studies across multiple investigators. Impact. Our goal is to characterize how different stakeholder values can and should be incorporated in the design and assessment of future non-therapeutic invasive human neurophysiological studies, with the anticipation that such perspectives will lead to more consistent, socially inclusive, and ethically rigorous risk/benefit assessments.